The biochemical aspect of this research proposal concerns investigation of factors or agents which control and modulate the release of arachidonic acid (AA) and the three major metabolic pathways of AA to thromboxanes, prostacyclin and prostaglandins in the subcellular fractions of the blood vessels. Further investigations of the release and the ultimate fate of these vasoactive lipids will then be related to the possible physiological mechanisms in the regulation of blood pressure and vascular reactivity. Subcellular fractions of the tissue (mesenteric blood vessels, aortas) will be used for assays of the enzymes (phospholipase, PG synthetase and cyclo-oxygenase, thromboxane synthetase and prostacyclin synthetase) which are intimately involved in the biosynthesis of these substances. The endoperoxide intermediate PGG2 and PGH2 will be isolated and its biological activity evaluated. In the study of prostaglandin metabolism, 14C or 3H labeled PG will be used as substrate, and the activities of the metabolic enzymes (15 OH-dehydrogenase, delta 13,14 reductase and PGE 9-ketoreductase) will be measured. The sensitivity of the PGE 9-ketoreductase to different vasoactive peptides and cyclic nucleotides will be given special attention. These experiments are designed to relate disorders of thromboxane, prostacyclin and prostaglandin biosynthesis or metabolism to diseases of the heart and blood vessels.